PROJECT SUMMARY/ABSTRACT Each year approximately 700,000 American children are identified as victims of maltreatment and evidence suggests that as few as 5% of abuse cases are reported. It is well established that children who experience maltreatment are at high risk for the development of psychiatric disorders, as well as major medical conditions including obesity, diabetes, and cardiovascular disease. Emerging evidence suggests that physiological change to neuroendocrine and immune systems is a major mechanism of the lasting impact of maltreatment on health. It is difficult to alter the trajectory of biological dysfunction in children and adults already diagnosed with health conditions, which suggests that a solution to the problem of mental and physical illness following maltreatment lies in understanding how it first emerges, and most importantly, which factors predict biological precursors to disease. Self-regulation, including emotional and physiological components, dictates an individual?s conscious or unconscious efforts to control their response to stress, and thus may be a critical mechanism linking maltreatment to biological precursors?inflammation, methylation of cytokine genes, and cardiometabolic symptoms?associated with future health conditions. No study to date has focused on emotion regulation and physiological arousal as central, modifiable mechanisms of the association between maltreatment and these three biological precursors. The overall aims of this study are to test whether emotion regulation and physiological arousal measured in naturalistic settings link childhood maltreatment to inflammatory proteins, epigenetic change of cytokine genes, and cardiometabolic symptoms. This innovative study will identify how self-regulation and biological markers precipitate the onset of disease in a vulnerable population. Importantly, self-regulation can be altered, and thus serves as a clear point of entry for future prevention and intervention programs to support children with a maltreatment history. This study will utilize comprehensive assessments of child maltreatment, novel approaches to self-regulation, and gold-standard measures of biological precursors. This highly structured training plan is ideally suited to allow for execution of the proposed research project. Specifically, the applicant will receive training in (1) developmental and biopsychosocial approaches to child maltreatment, (2) naturalistic observation and coding of emotion regulation and measurement and analysis of physiological arousal, (3) inflammation and epigenetic regulation of the immune system, (4) cardiometabolic risk, (5) advanced statistical analysis skills, and (6) dissemination, manuscript preparation and grant writing skills. Training will be guided by an outstanding mentorship team with highly relevant expertise and a long-standing history of collaboration. Therefore, the proposed training and research plans along with the rich training environment available at the Department of Psychiatry and Human Behavior of the Alpert Medical School of Brown University/Bradley Hospital will provide the applicant with experiences tailored to help her reach her ultimate goal of becoming an independent investigator.